The use of sustained-release drug dosage units for the oral administration of drugs to a patient has several therapeutic advantages. A therapeutically effective systemic level of a drug can be maintained over an extended time period without the necessity of multiple daily drug administration. Some drugs are toxic or otherwise deleterious in high concentrations, and thus require multiple administration of low-level amounts of these drugs to patients. Such administration results in a bolus rise in drug concentration initially, above the most effective therapeutic level, and a concomitant decrease over time below this level, producing a high-low fluctuation in blood levels of the drug. Sustained-release dosage forms overcome this problem by releasing the drug in small amounts throughout a predetermined time period and thus maintaining the drug level in the blood within a narrow therapeutically effective range as the rate of drug release and systemic drug removal are maintained in balance.
Numerous methods and compositions for preparing controlled-release drug compositions are known, and include those described in U.S. Pat. No. 4,572,833 to Pedersen, et al.; U.S. Pat. Nos. 4,713,248 and 4,716,041 to Kjornaes, et al; U.S. Pat. No. 4,772,475 to Fukui, et al.; U.S. Pat. No. 4,756,911 to Drost, et al.; U.S. Pat. No. 4,786,506 to Fontanelli; U.S. Pat. No. 4,351,825 to Southman, et al; U.S. Pat. No. 4,252,786 to Weiss, et al.; U.S. Pat. No. 4,199,560 to Gyarmati, et al; and Colombo, et al., European Patent Application No. EP0092060.